Network pharmacology-based strategy to investigate the bioactive ingredients and molecular mechanism of Evodia rutaecarpa in colorectal cancer.

BACKGROUND: Evodia rutaecarpa, a traditional herbal drug, is widely used as an analgesic and antiemetic. Many studies have confirmed that Evodia rutaecarpa has an anticancer effect. Here, our study explored the bioactive ingredients in Evodia rutaecarpa acting on colorectal cancer (CRC) by utilizing network pharmacology. METHODS: We clarified the effective ingredients and corresponding targets of Evodia rutaecarpa. CRC-related genes were obtained from several public databases to extract candidate targets. Candidate targets were used to construct a protein-protein interaction (PPI) network for screening out core targets with topological analysis, and then we selected the core targets and corresponding ingredients for molecular docking. Cell proliferation experiments and enzyme-linked immunosorbent assays (ELISAs) verified the anticancer effect of the bioactive ingredients and the results of molecular docking. RESULTS: Our study obtained a total of 24 bioactive ingredients and 100 candidate targets after intersecting ingredient-related targets and CRC-related genes, and finally, 10 genes-TNF, MAPK1, TP53, AKT1, RELA, RB1, ESR1, JUN, CCND1 and MYC-were screened out as core targets. In vitro experiments suggested that rutaecarpine excelled isorhamnetin, evodiamine and quercetin in the inhibition of CRC cells and the release of TNF-α was altered with the concentrations of rutaecarpine. Molecular docking showed that rutaecarpine could effectively bind with TNF-α. CONCLUSION: The pairs of ingredients-targets in Evodia rutaecarpa acted on CRC were excavated. Rutaecarpine as a bioactive ingredient of Evodia rutaecarpamight effectively inhibit the proliferation of CRC cells by suppressing TNF-α.

A novel 3'tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer.

At present, it is commonly believed that tRFs and tiRNAs are formed by the specific and selective shear of tRNAs under certain pressure stimulation, rather than by random degradation of tRNA. tRFs and tiRNAs have been reported to contribute to the biological process of a variety of human cancers. However, the evidence for the mechanisms of tRFs and tiRNAs in the occurrence and development of gastric cancer (GC) is still insufficient. Here, we aimed to explore the carcinogenic roles of tRFs and tiRNAs in GC with RNA-sequencing technique, and found a novel 3'tRNA-derived fragment tRF-Val was significantly upregulated in GC tissues and cell lines. tRF-Val expression was positively correlated with tumor size and the depth of tumor invasion in GC tissues. Functionally, tRF-Val promoted proliferation and invasion, and inhibited apoptosis in GC cells. Mechanistically, tRF-Val directly bound to the chaperone molecule EEF1A1, mediated its transport into the nucleus and promoted its interaction with MDM2 (a specific p53 E3 ubiquitin ligase), thus inhibiting the downstream molecular pathway of p53 and promoting GC progression. These findings provided a new potential therapeutic target for GC and a new explanation for the occurrence of GC.

Case Report: Abdominal Cocoon With Jejuno-Ileo-Colonic Fistula.

Introduction: Abdominal cocoon is a unique peritoneal disease that is frequently misdiagnosed. The occurrence of the abdominal cocoon with a jejuno-ileo-colonic fistula has not been previously reported. Case Presentation: We admitted a 41-year-old female patient with an abdominal cocoon and a jejuno-ileo-colonic fistula. She was admitted to our hospital for the following reasons: "the menstrual cycle is prolonged for half a year, and fatigue, palpitations, and shortness of breath for 2 months". On the morning of the 4th day of admission, the patient experienced sudden, severe, and intolerable abdominal pain after defecating. An emergency abdominal CT examination revealed intestinal obstruction. Surgery was performed, and the small intestine and colon were observed to be conglutinated and twisted into a mass surrounded by a fibrous membrane, and an enteroenteric fistula was observed between the jejunum, ileum, and sigmoid colon. We successfully relieved the intestinal obstruction and performed adhesiolysis. The patient was discharged from our hospital on the 6th postoperative day, then she recovered and was discharged from Feicheng People's Hospital after another 11 days of conservative treatment, and she recovered well-during the 2-month follow-up period. Conclusion: Abdominal cocoon coexisting with a jejuno-ileo-colonic fistula is very rare. During the process of abdominal cocoon treatment, the patient's medical history should be understood in detail before the operation, and the abdominal organs should be carefully evaluated during the operation to avoid missed diagnoses.

Impact of preceding noncurative endoscopic submucosal dissection on patients with early gastric cancer who undergo subsequent surgery: a meta-analysis.

BACKGROUND: The influence of preceding noncurative endoscopic submucosal dissection (ESD) on the efficacy of subsequent surgery is still controversial among early gastric cancer (EGC), especially for laparoscopic gastrectomy. The present meta-analysis was conducted to compare clinical outcomes between patients with EGC who underwent noncurative ESD before surgery (ESD group) and those who underwent direct surgery (non-ESD group). METHODS: Related databases were searched, and articles comparing differences between ESD and non-ESD groups were included for meta-analysis. RESULTS: Ten retrospective studies with 3465 participants were included in this meta-analysis. Compared with the non-ESD group, the ESD group was older and had more males, smaller tumors, more differentiated tumors and a higher proportion of pT1b, a shorter operation time, fewer dissected lymph nodes, a lower rate of positive lymph nodes and a lower rate of D2 dissection. There was no significant difference in intraoperative blood loss, postoperative complication rate, postoperative hospital stay or long-term prognosis, etc. CONCLUSION: Preceding noncurative ESD has no negative impact on the short- and long-term results of additional gastrectomy (open surgery or laparoscopic surgery).

CCDC12 promotes tumor development and invasion through the Snail pathway in colon adenocarcinoma.

Integrative expression Quantitative Trait Loci (eQTL) analysis found that rs8180040 was significantly associated with Coiled-coil domain containing 12 (CCDC12) in colon adenocarcinoma (COAD) patients. Immunohistochemical staining and western blotting confirmed CCDC12 was highly expressed in COAD tissues, which was consistent with RNA-Seq data from the TCGA database. Knockdown of CCDC12 could significantly reduce proliferation, migration, invasion, and tumorigenicity of colon cancer cells, while exogenous overexpression of CCDC12 had the opposite effect. Four plex Isobaric Tags for Relative and Absolute Quantitation assays were performed to determine its function and potential regulatory mechanism and demonstrated that overexpression of CCDC12 would change proteins on the adherens junction pathway. Overexpressed Snail and knocked down CCDC12 subsequently in SW480 cells, and we found that overexpression of Snail did not significantly change CCDC12 levels in SW480 cells, while knockdown of CCDC12 reduced that of Snail. CCDC12 plays a significant role in tumorigenesis, development, and invasion of COAD and may affect the epithelial to mesenchymal transformation process of colon cancer cells by regulating the Snail pathway.

Isolated synchronous Virchow lymph node metastasis of sigmoid cancer: A case report.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. Lymphatic metastases of this tumor are mostly confined to the regional lymph nodes, and distant supraclavicular lymph node metastases are very rare. CASE SUMMARY: In this report, we describe a patient with sigmoid carcinoma and isolated synchronous supraclavicular lymph node metastases. A 56-year-old male presented with a left cervical mass that was confirmed as a lymph node metastasis from sigmoid cancer by several auxiliary examinations. After 6 cycles of chemotherapy with the 5-fluorouracil, leucovorin and oxaliplatin + cetuximab regimen, the sigmoid colon tumor and Virchow's lymph node metastasis were significantly smaller than before treatment, and no new metastatic sites were observed. Considering the effects of chemotherapy on quality of life, resection of the primary tumor was performed followed by 4 cycles of chemotherapy with the original chemotherapy regimen. Virchow's lymph node dissection was selected by mutual consultation between the patient and us. After the second surgery, the patient received capecitabine and cetuximab chemotherapy and did not experience recurrence or metastasis during follow-up. CONCLUSION: In conclusion, supraclavicular lymph node metastasis without any other solid organ metastasis is a potential metastatic pathway for CRC. In addition, after resection of the primary lesion, postoperative chemotherapy combined with supraclavicular lymph node dissection is feasible for the treatment of patients with CRC and isolated synchronous Virchow's lymph node metastases.

A new candidate oncogenic lncRNA derived from pseudogene WFDC21P promotes tumor progression in gastric cancer.

As oncogenes and tumor suppressor genes, long non-coding RNAs (lncRNAs) regulate the biological behavior of gastric cancer (GC) cells such as proliferation, invasion, and metastasis through various signal pathways. At present, although numerous lncRNAs that significantly influence the development and progression of GC have been identified, a considerable number of them have not been found and studied yet. In this study, we identified a new lncRNA derived from pseudogenes WFDC21P, which have not been reported in any previous GC study. LncRNA WFDC21P was significantly upregulated in GC cells and tissues, and clinically associated with the pathological stages of advanced GC. WFDC21P promoted proliferation and metastasis of GC cells both in vitro and in vivo. LncRNA WFDC21P was directly bound to GTPase Ran and it promoted the activity of the Akt/GSK3ß/ß-catenin pathway. Forkhead Box P3 (FOXP3), as a transcription factor of WFDC21P, was directly bound to the promoter region and it positively regulated the transcription of WFDC21P. This finding may provide a novel biomarker and therapeutic target for GC.

Safety and efficacy of indocyanine green fluorescence imaging-guided radical gastrectomy: a systematic review and meta-analysis.

BACKGROUND: The clinical value of indocyanine green (ICG) in laparoscopic radical gastrectomy remains controversial. We performed this meta-analysis to investigate the safety and efficacy of ICG fluorescence imaging-guided radical gastrectomy. METHODS: All relevant studies published until 30 October 2020 were retrieved from several databases. Fixed- and random-effects models were used to analyze the results based on different heterogeneity levels. Data were expressed as odds ratios or weighted mean differences along with 95% confidence intervals. The Grading of Recommendations, Assessment, Development, and Evaluation system scale was used for quality of evidence evaluation. RESULTS: This meta-analysis included six cohort studies that investigated 622 patients. Compared with conventional radical gastrectomy, ICG fluorescence imaging-guided gastrectomy facilitates complete lymph node dissection, reduces intraoperative blood loss, and shortens the length of postoperative hospitalization. Moreover, we observed no significant intergroup differences in the operative time, first exhaust time, and postoperative complications. CONCLUSION: ICG fluorescence imaging-guided radical gastrectomy scores over conventional gastrectomy and appears to be a promising approach in patients who require radical gastrectomy. However, further research is warranted to explore the potential long-term survival benefit of ICG fluorescence imaging in patients with gastric cancer.

Case report of ascending colon cancer and multiple jejunal GISTs in a patient with neurofibromatosis type 1 (NF1).

BACKGROUND: NF1(Neurofibromatosis type 1) is an autosomal dominant genetic disorder. Patients with NF1 have an increased risk of developing benign or malignant tumours, such as gastrointestinal stromal tumours (GISTs). However, the coexistence of NF1, GIST and colon cancer is very rare, and few cases have been reported in the literature. CASE PRESENTATION: We admitted a case of a 64-year-old man with type 1 neurofibromatosis, GISTs, and ascending colon cancer. This case was characterized by café-au-lait macules, discrete cutaneous neurofibromas, nodular neurofibromas, multiple jejunal tumours, and ascending colon cancer. Laparoscopic exploration revealed ascending colon cancer and multiple jejunal tumours. Laparoscopic right hemicolectomy and local excision of the jejunal tumours were performed successfully. The pathological results confirmed moderate differentiated adenocarcinoma of the ascending colon with multiple jejunal GISTs (low risk, very low risk). Moreover, the immunohistochemistry results of multiple jejunal GISTs suggest that NF1 is positive. Whole-exome sequencing (WES) of colon cancer revealed mutations in more than 20 genes, including KRAS, PIK3CA, APC, SMAD4, etc. The results of whole-exome sequencing (WES) of jejunal GISTs revealed an NF1 mutation and no KIT or PDGFR gene mutation. CONCLUSION: We report a rare case of simultaneous NF1, GIST and colon adenocarcinoma. For patients with NF1, benign and/or malignant tumours are often combined. Therefore, these patients should undergo regular physical examinations so that early detection and early treatment can be achieved.